title: MAL hypermethylation is a tissue-specific event that correlates with MAL mRNA expression in esophageal carcinoma.
abstract: MAL promoter hypermethylation was examined in 260 human esophageal specimens using real-time quantitative methylation-specific PCR (qMSP). MAL hypermethylation showed highly discriminative ROC curve profiles which clearly distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding NE. There was a significant correlation between MAL hypermethylation and BE segment length. Treatment with 5-aza-2'-deoxycytidine reversed MAL methylation and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs with unmethylated MAL were significantly higher than in EACs with methylated MAL. MAL hypermethylation is a common, tissue-specific event in human EAC and correlates with clinical neoplastic progression risk factors.
authors.affiliation: 1] Department of Pathology, The Shenzhen University School of Medicine, Shenzhen, Guangdong, People's Republic of China [2] Shenzhen Key Laboratory of Micromolecule Innovatal Drugs, Shenzhen, Guangdong, People's Republic of China [3] Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, People's Republic of China [4].
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yulan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Xianling
authors.initials: X
authors.lastname: Feng
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Cao
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: Huimin
authors.initials: H
authors.lastname: Yu
authors.forename: Zhenfu
authors.initials: Z
authors.lastname: Zhao
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Mori
authors.forename: Xinmin
authors.initials: X
authors.lastname: Fan
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001471:Barrett Esophagus / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation; D000077209:Decitabine; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000235:genetics*; D060787:Neoplasm Grading; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; C569026:MAL protein, human; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine